Amplified Production of a DNA Decoy Catalyzed by Intracellular MicroRNA

AbstractDNA decoys inhibit cellular transcription factors and are expected to be among the nucleic acid drugs used to downregulate the transcription process. However, spatially controlling the on/off efficacy of DNA decoys to avoid side effects on normal cells is challenging. To reduce undesired decoy function in normal cells, we adopted catalytic hairpin assembly (CHA) to produce a DNA duplex from a hairpin DNA pair in response to a specific microRNA (miRNA). We designed the DNA hairpin pairs to form a DNA decoy that binds to nuclear factor kappa B (NF‐κB), whose overexpression is related to many diseases, including cancer. The transformation of the DNA hairpin pair to the NF‐κB DNA decoy was catalyzed by miR‐21, which is expressed in various types of cancers. Intracellular CHA progression and the inhibitory effect against NF‐κB were observed only in miR‐21 overexpressing cancer cells. The intracellular miR‐21‐catalyzed production of the NF‐κB DNA decoy has the potential to reduce side effects on normal cells, thereby strengthening the therapeutic profile of the CHA‐decoy system. The ability to customize the combination of catalytic miRNA and target transcription factors would allow our technology to serve as a “personalized drug discovery system” for a variety of challenging diseases, including cancer.